Time for the Big Talk. How's the CAA doing?

They have made only a few statements on XMRV (which is one reason I questioned Koan's choice of the word repeatedly - they have not done that much). I thought Dr. Vernon's statement 'XPlained' was well done; she stated XMRV could be the game changer that we've been waiting for while highlighting the need for replication and more information.

The CAA asked for an official statement from the National Cancer Institute on XMRV - good for them - nobody else thought to do that.

The CAA listed the prostate study as the example of what can go wrong when different studies used different techniques. In light of that they said they were working to try to ensure that other studies use the same subset of patients to replicate the WPI study. This is a problem because the CDC very likely doesn't have the information to ensure that those types of patients are being tested.

Too careful? - I don't see a pattern of trying to discredit this research. I see an organization being careful - once again, probably being too careful for most patients tastes - something has hurt them in the past and will probably hurt them now. They're obviously not being cheerleaders but if you look at other statements from prominent support groups in the UK I think you'll find similar statements.

C- I certainly wouldn't give them an F. I would probably give them a C-because they have not stepped forward in several ways. They are not, for instance, a real information source on XMRV - which they should be; they should have several sections on their website discussing all the different aspects of XMRV.

In that sense they're not relevant in a way they really should be. That continues to be a real problem for them. They are not necessarily the place to go for information. (That said none of the support groups either here or in the UK are - for XMRV - none of the organizations really picked up the ball. The IACFS/ME didn't even issue a statement for almost 2 weeks and then it was very paltry).

I would characterize them as being more than a bystander that's for sure but as the central source that they should be - no.

The Association has emphasized the need for replication studies to use similar laboratory methods and to select patients with characteristics similar to those in the WPI's XMRV study.

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There is nothing in there that discredits the WPI study. It's simply stating that there were very specific characteristics in that first group - the immune findings, low VO2 max findings plus the fact that everyone had to meet both the CDC criteria and the Canadian consensus criteria - that needs to be met for the study to be replicated.

If Bill Reeves tries to use his empirical definition defined patients to get these results he's probably not going to get them. Most researchers will have to go back and see which patients meet this criteria. Most of them probably don't have any information on whether somebody met the Canadian consensus definition.

As Joey recounted Dr. Peterson told him that he specifically looked for patients that he thought would be positive for XMRV; they were very ill, they had specific immune abnormalities, etc. It maybe a significant subset but it is not your typical chronic fatigue syndrome patient. I think that is where much of the worry comes in from the research community. That's why everybody's called for doing the test in less severely ill patients.

I know that Dr. Mikovits has said she thinks it will be found in most patients.

So there are two things - trying to find patients that met WPI's criteria for that first study and then expanding the study to include more patients.

Cort, I'm not advocating a litmus test. I understood why they were trying to work within the CDC that they had, and while I didn't like the Faces of CFS thing, I wasn't going to condemn the CAA for it. What bothered me was being instructed to lead patients to information that seemed, at the very least, inaccurate.

But I did not think much of it beyond that particular interaction. I've been a member for years. I know how much they've done for the good. But there's something about this response that bothers me. You mention that Dr. Vernon is tepid on it, and that's coming through. I'm wondering why they are not working with the WPI to get their answers instead of jabbing at them from the outside. And maybe they are trying to, but that's not clear.

I'm in no way suggesting that they mean anything but the best, or that their dedication is anything but strong. But this:

<blockquote>
We're hardly trying to rain on the parade -- we're trying to construct a tarp large enough to protect the community if rain should fall. With the experience of 22 years, the Association and this community have certainly weathered other similar storms, but we're doing what we can to prevent another.</blockquote>

troubles me.It strongly implies that there is protecting to be done. They sound like the overprotective mother who prophesizes doom and failure every time you try to do anything, and sends you lots of email forwards to back up her case. ("See, I TOLD you using that fancy deodorant would give you cancer!)

And I do think that there is something harmful in publicly echoing the criticisms of Bill Reeves. It gives all of his words more credence, and given how harmful some of them are, we do not need that. Suddenly, the CDC *and* the CFIDS Association are publicly criticizing the study? That changes the perception. They are our political arm and should understand the implications.

Cort, I think you are a wonder and I respect everything you've done and have learned so much. I don't mean any of this in anything outside of the spirit of discussion.

There are plenty of people, many at the CDC it must be said, who are willing to publicize the following. Why is the CAA doing it? What's the point? Is this what being "cautious" looks like or is this sowing seeds of doubt?

We are each entitled to our own opinion but the CAA contributions to the XMRV dialogue on Facebook are consistenly doubtful.

Posts from CAA on Facebook

The CFIDS Association of America
The Association has emphasized the need for replication studies to use similar laboratory methods and to select patients with characteristics similar to those in the WPI's XMRV study. Here's a cautionary tale about why this is so crucial: h...ttp://www.sciencedaily.com/releases/2009/10/091015191701.htm

The CFIDS Association of America
Other articles about the conflicting XMRV findings in prostate cancer have appeared in The Scientist
(h..p://www.the-scientist.com/blog/display/56062), the LA Times h..p://latimesblogs.latimes.com/booster_shots/2009/10/viral-link-to-prostate-tumors-questioned.html)

From another, longer, post in response to posters wondering why they are posting the above
"The German XMRV study was simply posted as a caution about how quickly headlines change as more studies are published. We are working vigorously to help the researchers genuinely interested in replicating the XMRV tests have the best opportunity to do so. WPI has been encouraged to publish its selection criteria for patients and controls and we hope they will. Age, sex, duration of illness, medication use, etc. are all important characteristics to control for in the next set of studies, especially since 20 of the 101 patients in the WPI study are reported to have lymphoma (but before or after the blood was drawn that was used for this study?)"

They go on to say they are trying to protect us. I have only my own opinion but I don't feel protected by this.

I feel as though good research, and fine researchers, are being called into question for absolutely no reason.

CAA even brings this into the mix:

The CFIDS Association of America
There are less responsible reports with very high circulation: h..p://www.naturalnews com/027277_cancer_Prostate. Headlines also get more attention than text. Conflicting data is a major source of the doubt and uncertainty that plagues CFS, undermines appropriate medical care and erodes social support.

Why give more space, as I have just done , to the opinions of Natural News on this particular matter? Why provide the link? I don't get it.

This is just FaceBook.

Ok, my stirring up a tempest in this particular teapot just contributes to the problem. I'm not suggesting they have malign intent. I'm suggesting only that they are incautious and not serving the greater needs of the community at this time.

Yes, studies need to be replicated. Yes, there is more to learn. Yes, these are early days. No, I don't need CAA to hammer that home. There are plenty of other people more than willing to do that. Lots of people will take away the message that this wasn't really worth much attention, that it's very preliminary, that it doesn't mean anything. That message does not serve us. Well, it doesn't serve me.

peace to all,
Koan

PS I do hope I have not trod on any toes. If I have, I am truly sorry, but I'm just sharing my one, perhaps insignificant, opinion.

ET underline what I see as "seeds of doubt" in the messages. All underlines mine.

Koan, that's what I mean, too. Why on earth post the German study as "a cautionary tale." What good does that do? Perhaps it's telling the community, "Don't get too excited," but all that does is create the perception that there's something to be wary of. And that does no good at all. I truly don't understand the purpose of these posts.

I'm in no way suggesting that they mean anything but the best, or that their dedication is anything but strong. But this:

<blockquote>
We're hardly trying to rain on the parade -- we're trying to construct a tarp large enough to protect the community if rain should fall. With the experience of 22 years, the Association and this community have certainly weathered other similar storms, but we're doing what we can to prevent another.</blockquote>

troubles me.It strongly implies that there is protecting to be done. They sound like the overprotective mother who prophesizes doom and failure every time you try to do anything, and sends you lots of email forwards to back up her case. ("See, I TOLD you using that fancy deodorant would give you cancer!)

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Yes, Anne, I read your post and wished I had been able to say it so well.

Merde! I cut off what you said next which, I believe, bears a second read. It does for me. I'll go back and read your original again.

I think it strikes us the same way and I think we each come from the same open minded place.

I have no history with them of any kind. I just don't get their attitude around this issue.

peace out all,
koan

ETA

The bit I accidentally cut out. Anne went on to say what I think is at the heart of this discussion:

And I do think that there is something harmful in publicly echoing the criticisms of Bill Reeves. It gives all of his words more credence, and given how harmful some of them are, we do not need that. Suddenly, the CDC *and* the CFIDS Association are publicly criticizing the study? That changes the perception. They are our political arm and should understand the implications.

I don't know whether my perspective will be helpful here or not, but I just want to share some experience.

I have worked as a scientist for over 40 years now. Most of that time was spent in the physical sciences rather than in the biological sciences, but I've found that they are very similar with respect to what I will comment on here.

In science, we are taught to be skeptical. Historically, this has served the scientific establishment in good stead. When someone performs a piece of scientific work, whether it is theoretical or experimental (or clinical, in the case of biomedicine) they really have to run a gauntlet that is set up by the scientific community, to find out if their work will stand up or not.

The first hurdle, if one is part of an institution, is to get approval from the management for the work to be submitted to a journal for publication, because the institution's reputation is on the line.

If it survives that, it is sent to the editor of a journal. Usually the most highly regarded journal that is thought likely to publish the work is selected.
One measure of the ranking of a journal is how often its papers have been cited in later work published in journals in general. If these numbers are large, it suggests that they have published something of fundamental importance in the particular scientific field.

If the editor thinks it's at least worthy of consideration, he (or she) sends it to anonymous reviewers, who critique it. Usually these reviewers are people who have experience in the same subspecialty as the work described in the paper. They are usually not compensated for this work, which can be difficult and time-consuming. Often, these reviewers are people who have alternative ideas, which they may have published, and sometimes they are competing for the same funding as the person who submitted the work. So this can be brutal, and sometimes the editor has to consult with additional reviewers to make a decision.

Sometimes the reviewers insist that major rewrites or additional scientific work be done before they will approve the manuscript. The latter can be expensive, and the researcher has to find the funds to do that.

Ultimately, the decision to publish is in the hands of the editor. He or she is motivated to publish important new work in their journal, but if something they publish turns out to be invalid, especially if it could have been detected in the review process and wasn't, it gives the editor and the journal a black eye. So this is not an easy job. Even the most highly regarded journals, such as Science and Nature, have made some blunders in the past, and of course, these journals compete with each other.

If a paper gets through this process and is published, it is then subjected to criticism by the scientific community as a whole, who are now able to read the paper, which was confidential until it was published, to prevent others from stealing the work and publishing first. You can see that there is a lot of trust involved here! -) Credit for discovery in science is determined by first date of publication in a peer-reviewed scientific journal. Things like Nobel prizes hang on this, so it's a big deal to scientists.

Criticism by the larger scientific community is the process that has been going on publicly (as well as behind the scenes) since the XMRV paper was published. A large number of scientists are scrutinizing it, and raising whatever issues they see as possible weaknesses in the work. This may seem negative and unhelpful, but it is an important part of the process of determining whether the work is actually valid scientifically. Most scientists do this out of the public eye. Organizations such as the CDC, the CFIDS Assn, the IACFS/ME, and the NCF, however, cannot keep a low profile during this process, because the public, the media, and/or their memberships demand that they make public statements. So they have to decide how to be properly skeptical from a scientific standpoint, while perhaps sounding somewhat optimistic, since neither they or anyone else at this point knows how this will finally come down. So they are in a tough position, also.

Some of you may recall the "Cold Fusion" fiasco from a few years ago. I was heavily involved in debunking that as part of my job working in that field at that time. This was a case of some work that was published in a peer-reviewed scientific journal (though as I recall the authors went public on TV before publication, which is considered a big No-No in scientific research), but it was unfortunately riddled with errors in experimental technique and interpretation. The scientific community, including the group I was part of, found many of them, and this paper was soundly discredited.

I have also been on the other end of this process. I've submitted papers to journals and had them rejected by the reviewers, sometimes for reasons that I didn't believe were scientifically valid. The recourse is to try a different journal, which will likely have different reviewers. However, each journal has its own format, so it can require a lot of rewriting to do this. Also, some journals charge fees for reviewing papers, and this money has to come from somewhere.

I guess what I'm trying to convey is that the scientific process is kind of brutal. There are some good reasons for that, and some that are not so good, having to do with the less desirable aspects of our human nature. But we haven't found a better way to arrive at truth about the natural world than this method. It's sort of like the statement about democracy not being so hot, but it's better than all the alternatives we have found. I realize that this is not an accurate quotation, but you get the idea.

From my point of view, the attitude we should have about the XMRV work is to be hopeful and optimistic, but at the same time, to be skeptical and to seek answers to the legitimate questions that arise about this work. It's sort of like President Reagan's philosophy in dealing with the Soviet Union: Trust but verify.

I'm not going to comment on the possible personal motivations of some of the personalities involved in the public comments about the XMRV work. No matter how these comments are motivated, I think we need to take an objective look at them, and if they raise issues that need to be settled in order to test the validity of these new results, then we should take them seriously and urge that they be studied properly to be answered. If they are just expressions of uninformed opinion, let them go on by, because uninformed opinion does not constitute evidence, which is what really counts in the application of the scientific method. In order to really get answers in CFS that will help to restore people to health, we need to be sure that we are operating from sound information.

I will say that this development has certainly livened up the public dialog about ME/CFS.

You should feel protected! There is nothing the matter with this statement. Did you read the second part of it? "to select CFS patients who are as similar as possible to the original group."

For example, we need to know the age, sex, duration of illness, medical history, and medication use – to name a few characteristics – of the studied patients to select CFS patients who are as similar as possible to the original group.

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They want to get as close as possible to the original cohort to ensure that the study is replicated. Science did a lousy job at providing information- they're not that kind of journal; they often don't provide alot of information. There is nothing the matter with asking for more information.

Where did the idea that they are is 'publicly echoing' the ideas of Dr. Reeves? Talk about the power of words;we went from several researchers coming up with independent sets of question to the idea that Dr. Reeves said something and the other researchers are 'echoing him'. That's not fair.

Yes, be wary - The fact is that there is something to be wary of; until any study is replicated there are many things to be wary of. Take the Pacific Fatigue Labs first study on repeat exercise tests- the percentage of patients with abnormal results went from 90% to 50% on the next study and that study was still on an unusual subset. It may drop even lower.

Lactic acid - went from almost all CFS patients to very few on the next study. A similar curve was seen with enteroviruses. Remember hypercoagulation? That went from the in thing to no-thing; they all got screwed up on the second study.

Select Start The problem is that the first group tends to be a very select one - as I put it before - the first researcher 'stacks the deck' - they select the worst off patients and use them for it. Dr. Peterson in fact stated that that''s what he did - its what they almost ALL do (actually except the CDC, ironically enough). If 20% of your initial study has lymphoma - that went from a subset to a very unusual subset - that is not your typical CFS patient.

I agree this was not so good (or very well written!):

There are less responsible reports with very high circulation: h..p://www.naturalnews com/027277_cancer_Prostate. Headlines also get more attention than text. Conflicting data is a major source of the doubt and uncertainty that plagues CFS, undermines appropriate medical care and erodes social support.

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but I'll also point out that the CAA's tone in general has been moderate and their questions are not unique to them (or Dr. Reeves). I do think they got a little defensive in some of their answers.

It's a tricky time - everyone's very excited. But how to bring everybody down to earth a little bit (which I believe is appropriate) without being perceived as a naysayer or a party pooper?; apparently they didn't do that very well!

Anne and Koan: Please don't take what I say personally. I really appreciate the constructive atmosphere of this forum and always like to read your thoughts.

I can't quite agree with you on this one, though. Even after reading the statement in question (Facebook post on the German study) several times, I can't see how this should discredit WPI in any way.

In fact I perceive it as being cautious in the right way, and there definitely is still a lot to be cautious about. This is too huge for all of us: Imagine if everyone jumped on board and agreed that "This is it", and then after a few weeks or months it turned out that it wasn't! I read the NCI guidelines today, and to me THEIR statement sounded a lot more cautious regarding the meaning of their findings. Cautious, but not destructive or critical. There still IS so much we don't know yet.

An institution like the CAA is one of the places that everybody turns to, well at least I do, to see how they react. If they react entirely optimistic, I tend to let my guard down and be swept away by hope and trust in a good future. To find out that it might not imply what we now think it does would really devastate me.

Now I know I'm a grown-up person, I make my own judgements, but still what people like those at the CAA think matters to me, matters greatly. I WANT them to be realistic, and in my opinion, that's all they are.

Not to worry, Nina, I don't take what anyone says personally. I'm happiest in an atmosphere of lively discourse.

I appreciate Rich's comments, as always, and also welcome scientific rigor. You will not see me getting tested or taking anti-virals any time soon. I am the ultimate skeptic.

I know nothing about CAA. It's not on the radar of Canadians the way it is below the 49th. I get the feeling that there are factions and politics but I don't know what they are or who aligns with whom.

I do understand the role the CDC has played in the global understanding of an illness I have had for 30 years. I've kept abreast of their shenanigans.

What I have read lately from the CAA has left me thinking, with no knowledge aforethought, that they were not all that supportive of efforts to continue the exciting research into XMRV at WPI. I will grant that I may be completely wrong about that but I, and many others, were left with that impression.

If those of us who know nothing about them, along with some who do, are left feeling that they are more than a little critical of WPI methods, that is significant. It does not mean, of course, that they are but it does mean that they are giving that impression.

Please remember, I am totally and blissfully unaware of any history or politics. Is the impression I got the one they wish to give because its the one I got.

ok, you have all had plenty of me!

peace out!
k

ETA I know, I know, how can they seem unsupportive of continuing research when they are talking about continuing research. What I am saying is that they do not seem to be part of the engine underneath it. They do not seem to be giving energy to moving forward.

I find it really annoying when people post and then fiddle around with it but I did. I'm bad.

You wrote, "As Joey recounted Dr. Peterson told him that he specifically looked for patients that he thought would be positive for XMRV; they were very ill, they had specific immune abnormalities, etc. It maybe a significant subset but it is not your typical chronic fatigue syndrome patient. I think that is where much of the worry comes in from the research community. That's why everybody's called for doing the test in less severely ill patients."
===============
Not everybody! I think I can speak for some of the most severely ill patients when I say that they hate that they are the ones who have been excluded from most studies in the past. They are too sick to get to a doctor's office, too sick to fill out forms, perhaps too sick to even talk on the phone.

So when you say that "everybody" is calling for tests in less severely ill people, who is "everybody?" Is it people who want to disprove that XMRV is linked to severe illness?

In my opinion, if the "typical" CFS patient is used, and not the severely ill patients used in the WPI study, then there is no way you can say the study is being replicated.

This does bring things into perspective. Still......it is very exciting.

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Frickly,

What Rich said makes it even more exciting! I love being reminded of how many hurdles and hoops must be got through before publication. To remember that and the fact that two other institutions were willing to have their names connected to it... well!

I think I can speak for some of the most severely ill patients when I say that they hate that they are the ones who have been excluded from most studies in the past. They are too sick to get to a doctor's office, too sick to fill out forms, perhaps too sick to even talk on the phone.

So when you say that "everybody" is calling for tests in less severely ill people, who is "everybody?" Is it people who want to disprove that XMRV is linked to severe illness?

In my opinion, if the "typical" CFS patient is used, and not the severely ill patients used in the WPI study, then there is no way you can say the study is being replicated.

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Yes. Exactly. Thank you for this, Advocate. You certainly speak for me.

My greatest fear is that follow-up studies might include that "typical" patient way too early in the game.

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I have thought about this often, and echo these sentiments as well. Which is where it would seem Bill Reeves has the greatest ability to throw a monkey wrench into things. If he uses his own definition of ME/CFS in any CDC research efforts, it's virtually assured they will not replicate the WPI results.

However, I believe future XMRV research will likely bring in many new players (individuals and/or organizations) and eventually overshadow some of the major players that have been prominent in the past. Past players who have been able to often unduly shape public policy and perception on ME/CFS.

So even though I've enjoyed this thread and have learned a lot, I don't know how relevant it will all be going forward. Individuals and/or organizations that may not have always acted in our best interests (probably often innocently so), just won't have as much clout going forward. The science will eventually end up being too big for this to happen. I do believe we are in a new era where the past may not be able to repeat itself.

BTW, I tend to give the benefit of the doubt to people and/or organizations when it comes to trying to discern their true intent. In the case of CAA, I can see why there are legitimate concerns about their intent. But I guess I'll err on the side of believing they are probably doing the best they can for us. We all have our blind spots and areas of lack of awareness. It just simply not easy being fallible human beings.

So even though I've enjoyed this thread and have learned a lot, I don't know how relevant it will all be going forward. Individuals and/or organizations that may not have always acted in our best interests (probably often innocently so), just won't have as much clout going forward. The science will eventually end up being too big for this to happen. I do believe we are in a new era where the past may not be able to repeat itself.

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This was what I was sitting here thinking and did not have the brain to put into words. Ditto and thanks!

So on the one hand you say that the NCF [National CFIDS Foundation] is skeptical of the XMRV findings. On the other hand you say that the NCF's favorite hobby is bashing groups, individuals, etc.

Doesn't this suggest that if we are to be consistent that we should not give much weight to the NCF's skepticism?

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After reading the newsletter for about a year and a half, I stopped giving much weight to anything they said. Everything was downbeat, just constantly negative, with no hope until THEY find the cure.

My main point was only that the NCF's initial reactions regarding the WPI's study makes the CAA look like saints. The NCF's email also said that "some" (in their circle of advisors) were even 'questioning' the fact that one of the study's authors is also the owner of the only lab that will profit from the demand for tests. That's almost in line with what the "NaturalNews" article was suggesting...

I would point out that that the fear that the replication studies would include different types of CFS patients was exactly what the CAA was worried about. That was why they wanted more information:

The design of replication studies should include CFS patients who are similar to those selected by Dr. Peterson and reported in the Science study. Unfortunately, the details about the CFS patients were not sufficient to enable independent investigators to select similar CFS patients.

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The WPI has now provided those details.

Plus

Independent replication studies should also include patients with mild and moderate CFS, at least one chronic disease control group (e.g., multiple sclerosis, lupus) and sex and age-matched healthy controls. We are actively working with several independent research groups to expedite these studies.

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So there should be at least two types of studies; one on the original cohort and one on more typical patients.

(Hence the introduction of the XMRV prostate study - they used different techniques).